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Adrian was born at Hampstead, London to Alfred Douglas Adrian, CB MC, legal adviser to the Local Government Board and Flora Lavinia Barton.[3] He attended Westminster School and studied Natural Sciences at Trinity College, Cambridge, remaining in Cambridge for the major part of his life.

Completing a medical degree in 1915, he did clinical work at St Bartholomew's Hospital London during World War I, treating soldiers with nerve damage and nervous disorders such as shell shock. Adrian returned to Cambridge in 1919 and in 1925 began his studies of nerve impulses in the human sensory organs.

Continuing earlier studies of Keith Lucas, he used a capillary electrometer and cathode ray tube to amplify the signals produced by the nervous system and was able to record the electrical discharge of single nerve fibres under physical stimulus. An accidental discovery by Adrian in 1928 proved the presence of electricity within nerve cells. Adrian said,

"I had arranged electrodes on the optic nerve of a toad in connection with some experiments on the retina. The room was nearly dark and I was puzzled to hear repeated noises in the loudspeaker attached to the amplifier, noises indicating that a great deal of impulse activity was going on. It was not until I compared the noises with my own movements around the room that I realized I was in the field of vision of the toad's eye and that it was signaling what I was doing."

A key result, published in 1928, stated that the excitation of the skin under constant stimulus is initially strong but gradually decreases over time, whereas the sensory impulses passing along the nerves from the point of contact are constant in strength, yet are reduced in frequency over time, and the sensation in the brain diminishes as a result.

Extending these results to the study of pain causes by the stimulus of the nervous system, he made discoveries about the reception of such signals in the brain and spatial distribution of the sensory areas of the cerebral cortex in different animals. These conclusions lead to the idea of a sensory map, called the homunculus, in the somatosensory system.

Later, Adrian used the electroencephalogram to study the electrical activity of the brain in humans. His work on the abnormalities of the Berger rhythm paved the way for subsequent investigation in epilepsy and other cerebral pathologies. He spent the last portion of his research career investigating olfaction.